Human Participants and Sequencing

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CORE C, Human Participants and Sequencing: ABSTRACT The past decade has seen a rapid increase in diagnosis of genetic primary immunodeficiencies (PIDs) involving T lymphocyte dysfunction, in part due to the advent of population based newborn screening for severe combined immunodeficiency (SCID). This Program Project will combine new approaches that utilize deep sequencing, high-throughput cellular screening, genomics, gene editing, and functional testing in cellular systems and animal models to transform our understanding of human lymphocyte differentiation and function, and to create new, personalized treatments for affected individuals. The Projects and Cores of this Program will address the major challenges that have stood in the way of realizing this transformation by integrating clinical data from T-cell insufficient patients with basic investigations drawing on the expertise of leaders in immunology, bioinformatics, target validation, and genome editing. The Human Participants and Sequencing Core (Core C) serves the essential roles for the entire Program of (i) enrolling the human subjects, and (ii) conducting the deep sequencing. Subjects to be studied will be patients with T cell insufficiency or severe combined immunodeficiency (SCID) whose genetic diagnosis is unproven despite having had known genes responsible for these conditions investigated. Parents will be enrolled also. Core C will be the entry point and tracking hub for: informed consent, receiving samples, and collecting and recording phenotypic data (Aim 1); preparing samples for studies to be carried out by all the Projects and Cores (Aim 2); and obtaining special samples, including CD34+ primary cells from SCID patients for Projects 2 and 3 (Aim 3). Furthermore, Core C will obtain genomic DNA and cell-subset RNA sequencing for all Projects (Aim 2), sharing it, as permitted, with national databases to contribute to publicly available de-identified information on rare diseases (Aim 4).